Alpha 1 adrenergic receptor activation of proto-oncogene expression in arterial smooth muscle: regulation by nitric oxide and vascular injury.

Abstract

The role of the endothelium in modulating smooth muscle cell growth is unclear. alpha 1 adrenergic receptors activate proto-oncogene expression in smooth muscle. We have now found in rat aorta that carbachol, a muscarinic cholinergic agonist that promotes release of nitric oxide (NO), inhibits expression of c-fos and c-jun mRNA induced by alpha 1 receptors. NO synthase inhibitors blocked the effects of carbachol on c-fos mRNA and a cGMP analog mimicked carbachol. After balloon injury in rat aorta using in situ hybridization, the catecholamine-induced increase in c-fos mRNA expression in the medial layer was inhibited by the alpha 1 receptor antagonists, prazosin and chloroethylclonidine. In the neointima, this response was fully blocked by prazosin; however, chloroethylclonidine only partially inhibited it. These results suggest that NO, acting through a cGMP-dependent mechanism, inhibits expression of the c-fos and c-jun genes in arteries, which may contribute to the growth-inhibiting effects of the endothelium. After endothelial damage, the activation of c-fos in neointima by adrenergic stimulation may involve a subtype of alpha 1 receptor different from that utilized in medial smooth muscle.